Staphylokinase (hereinafter abbreviated as SAK) has no protease activity in itself, but is a kind of plasminogen activator similar to streptokinase (hereinafter abbreviated as SK) in that its complex with plasminogen or plasmin activates plasminogen. SAK has a molecular weight of about 15,000 and a size which is not greater than 1/3 of the size of SK. Since the genes have been cloned and their DNA sequences have been elucidated, it is considered that SAK is an appropriate substance for analyzing the action mechanism on a molecular level. The inventors of this application have proposed a method for collecting SAK accumulated in coliform bacilli which are integrated with SAK genes and cultivated (Japanese Patent Laid-open No. 58-67181). A major proportion of SAK obtained by the method is composed of a peptide which consists of 136 amino acid residues SEQ ID NO: 1 (Sako, T., Eur. J. Biochem., 149, 557-563(1985)).
It has been found that the action mechanism of SAK is different from that of SK. Especially, it has been confirmed that unlike SK, SAK has such a characteristic feature that the activity is increased in the presence of fibrin (i.e. fibrin specificity) and, thus, functions as a good thrombolytic agent (Japanese Patent Laid-open No. 63-90252). Also, in order to improve the delayed reactivity of SAK, there has been proposed a thrombolytic agent in which a complex of SAK and plasminogen (or fibrin) is preformed (Japanese Patent Laid-open No. 1-13044).
SAK composed of a peptide which consists of 136 amino acid residues obtained by the above-mentioned method is advantageous in that its molecular weight is smaller than other thrombolytic agents hitherto employed, ensuring good penetration into thrombi, coupled with another advantage that mass production by a simple manner is possible. This results in a better economy than in the case of other thrombolytic agents.
Although SAK composed of a peptide which consists of 136 amino acid residues has good characteristics as stated above, a smaller molecular weight is more preferable to prevent the occurrence of problems on antigenicity and dosage, etc.